Substance abuse directly affects the central nervous system of developing fetuses. Newborn infants, born of mothers using cocaine or methamphetamine, suffer withdrawal symptoms and may exhibit delayed development, seizures, and decreased motor skills development. The mechanisms by which particular populations of neurons are affected are unknown. Both cocaine and methamphetamine are known to affect dopamine containing neurons. Thus we, plan to establish dopamine neuronal cultures from specific areas of brain (substantia nigra and basal ganglia) as a model culture system. The effects of cocaine and methamphetamine on neuronal function will be assessed. Specifically, we will examine the effects of the drugs on: a) tyrosine hydroxylase enzyme activity, immunocytochemistry, and mRNA levels; b) on dopamine uptake and dopamine D2 receptor levels; and, c) on mRNA levels of the oncogenes, c-fos and c-jun. The oncogenes are elevated during seizures and may be involved in the regulation of delayed early genes, such as tyrosine hydroxylase. These studies should indicate the mechanisms of action of these drugs and may provide promising clues for treatment.